This application is a revision of a proposal submitted to NIDCD on June 1, 1992, for continued support of the University of Pennsylvania Smell and Taste Center, the first Clinical Research Center in the United States devoted to the study of the chemical senses. This interdisciplinary center was founded in 1980 with three major goals in mind: first, provide the physical resources and intellectual milieu for research activities related to the understanding, diagnosis, treatment, and management of chemosensory disorders; second, to provide clinical evaluation, treatment and counseling of patients experiencing such disorders; and third, to train scientists, clinician, and students in both basic and applied aspects of chemoreception science. In light of these goals, we will, during the coming grant period, (a) expand the database management capabilities of the Center's Core facility (a rich resource for study of the etiology, and natural history, clinical manifestations, and treatment of chemosensory disorders) and (b) embark on major new initiatives within each of four primary research areas: (i) Development and Application of Clinical Olfactory Diagnostic Tests, (ii) Magnetic Resonance Imaging of the Olfactory System (iii) Synaptic Organization of Excitatory and Inhibitory Centrifugal Inputs to the Main Olfactory Bulb and (iv) Neuroendocrine Factors and Brain Mechanisms in the Modulation of Olfactory test battery, (b) the quantitative analysis, using magnetic resonance imaging (MRI), of olfactory bulbs, tracts and higher brain regions in a number of patients groups with olfactory dysfunction (e.g., Alzheimer's disease, Parkinson's disease, head injury patients, and congenital anosmic), (c) an assessment of relationships between quantitative MRI measures and state-of-the-art psychophysical measures of olfactory function, (d) pre- and post-operative longitudinal assessment of olfactory function following resection of temporal and frontal cortical tissue in patients with intractable epilepsy, (e) evaluation of correlations among different types of olfactory tests (e.g., test of odor detection, discrimination and memory) in a wide variety of patient populations, including familial Parkinson's disease, amyotrophic lateral sclerosis, multi-infarct dementia, schizophrenia, retinitis pigmentosa, Usher's syndrome, and pseudohypoparathyroidism, (f) studies of the influences of dopaminergic and cholinergic drugs on taste and smell function of rats, (g) an assessment, in an animal model, of prophylactic influences of estrogens, corticosteroids, and antioxidants on olfactory dysfunction stemming from olfactotoxicants, and (h) an elucidation of specific anatomical relationships between (i) cholinergic and GABAergic centrifugal fibers and (ii) discrete neuronal populations within the olfactory bulb. Overall, these clinical and basic research programs will lead to a better understanding of the sense of taste and smell in health and disease, and to more effective diagnosis, management, and treatment of patients with chemosensory disorders.